Obesity is a serious medical problem: in the United States alone, it causes approximately 300,000 deaths and estimated healthcare costs in the amount of $100 billion per year. However, currently available therapy remains unsatisfactory. In this project, we propose to electrically stimulate the small intestine for the treatment of obesity. The feasibility of intestinal electrical stimulation has been demonstrated in Phase I of this project. The long-term aim is to develop an implantable stimulator for the treatment of patients with obesity using the proposed IES method. It is hypothesized that IES reduces weight by reducing food intake via its inhibitory effects on stomach motor functions and by reducing intestinal absorption via its excitatory effect on intestinal transit of nutrients. The specific aims of this project are to: 1) to test the functionality and reliability of a newly developed implantable stimulator in animals, 2) to optimize the performance of IES with various stimulation parameters in animals, 3) to investigate long-term efficacy and safety in reducing weight in animal models of obesity. A multidisciplinary team has been assembled with extensive knowledge and experience in engineering, physiology and clinical medicine related to device development, the gastrointestinal system, electrical stimulation, and obesity. Physiological experiments are designed to study the feasibility and to optimize the proposed method. A prototype implantable stimulator has been developed. The long-term efficacy and safety of the proposed method will be investigated using the stimulator in a porcine model. It is believed that the technology to be developed in this project will not only lead to a medical breakthrough for obesity but also greatly expand the applications of electrical stimulation to other areas related to the gastrointestinal tract. [unreadable] [unreadable] [unreadable]